Safety Evaluation of Ocular Drug Delivery Formulations: Techniques and Practical Considerations

Abstract

Development of new drug candidates and novel delivery techniques for treatment of ocular diseases has recently accelerated. Treatment of anterior-segment diseases has witnessed advances in prodrug formulations and permeability enhancers. Intravitreal, subconjunctival, and periocular routes of administration and sustained-release formulations of nanoparticles and microparticles, as well as nonbiodegradable and biodegradable implants to deliver drugs to the posterior segment of the eye, are becoming popular therapeutic approaches. Without adequate regulatory guidance for ocular drugs, such routes of administration and novel formulations can pose unique challenges to those involved in designing nonclinical programs, including considering clinical and nonclinical factors and choosing species, strains, and ocular toxicity parameters. Toxicologic pathologists also contribute practical experience to evaluating morphological effects of these novel formulations. Lastly, understanding species' anatomical differences is useful for interpreting toxicological and pathological responses to the eye and is important for human risk assessment of these important new therapies for ocular diseases.

Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone

“…Three methods are used for drug delivery to the posterior segment and fundus in clinical settings ( Figure 1). [1][2][3][4][5][6][7] The first method has been applied to the treatment of posterior segment disease and involves injection or implantation of the drug into the vitreous humor via the flat part of the ciliary body. The second method targets the subconjunctival fascia by implantation or injection, with the drug eventually becoming concentrated in the choroid, retinal pigment epithelium, retina, etc.…”

In vitro and in vivo evaluation of thermosensitive chitosan hydrogel for sustained release of insulin

“…In addition to the high probability of infection and surgical difficulties encountered with these implantable systems that restricts their application, the presence of a polymeric membrane could hinder appropriate release of large molecular weight drugs such as insulin (Short, 2008). These complications associated with implantable systems have led to investigations based on injectable in situ forming hydrogels as promising systems for controlled release of large molecular weight drugs (Ganji & VasheghaniFarahani, 2008;Yan et al, 2010).…”

Drops, Drops, and More Drops

“…(Vold and Buznego, 2010) Ocular implants can be placed in the sclera, subconjunctiva, intravitreal, or suprachoroid, and can be biodegradable or nonbiodegradable. (Short, 2008;Bourges et al, 2006;Choonara et al, 2009;Yasukawa et al, 2006) Miniaturization of the implants facilitates their delivery by direct injection. Medications can also be delivered by periocular injection, to facilitate drug delivery to the posterior segment of the eye, however repeated long-term injections can cause serious ocular complications.…”

“…Liposomes are designed to be injected into the eye, and offer the advantage of reduced toxicity since a limited amount of drug is in contact with ocular tissues. (Short, 2008) …”